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Highlights • EBV reactivation was observed in patients with COVID-19. • NK + and CD8 + T cell reduction was related to the severity of COVID-19 infection. • An increase of B cells in patients with severe symptoms was documented., Objectives The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

To characterize the antiviral effect and tolerability of higher dose (HD, 600 mg two times daily) and lower dose (LD, 400 mg two times daily) combination regimens of ritonavir and saquinavir in British Columbia (BC), Canada.Intent-to-treat analysis with suppression of plasma viral load to levels below 500 copies/ml as the main outcome measure.Adult human immunodeficiency virus (HIV)-positive individuals in the province of British Columbia prescribed ritonavir and saquinavir in combination between 1 September 1996 and 30 June 1997, with a minimum of two plasma viral loads, one at baseline and one after the initiation of therapy.A total of 84 participants [27 HD (32%) and 57 LD (68%)] were prescribed ritonavir and saquinavir. There was no difference at baseline in the two groups with respect to age (P=0.466), CD4 cell count (P=0.373) and baseline plasma viral load (P=0.656). However, LD were more likely to have had prior protease experience than HD participants (65 versus 40%, P=0.037). The median follow-up time was 9 months. A total of 44 (52%) subjects demonstrated a decrease in plasma viral load to levels500 copies/ml. After adjusting for length of follow-up, baseline CD4 cell count and prior AIDS diagnosis, HD participants were as likely to be suppressed to500 copies/ml as LD individuals (P=0.760). HD participants did report more adverse effects (P=0.042) than LD subjects.Our results provide confirmatory evidence that lower doses of ritonavir and saquinavir in combination are better tolerated and as effective as the standard doses of these drugs. This response, however, is seriously compromised by prior exposure to protease inhibitors.

The pharmacokinetics of nelfinavir tablets (A) and an oral simplified nelfinavir suspension (B) were studied. Twelve healthy volunteers randomly received either five 250-mg nelfinavir tablets or a simplified oral suspension obtained from tablets dissolved in water (nelfinavir 1250 mg in 100 mL of water) in a single dose before being crossed over to the second treatment after a one-week washout period. Blood samples were drawn up to 24 h after drug administration. Nelfinavir concentrations in plasma were analyzed by a specific and validated reverse-phase high-performance liquid chromatography assay (HPLC) with UV detection, and pharmacokinetic values were determined. For the AUC(0-infinity) with means+/-SD of 31.71+/-7.85, 30.88+/-10.28 (microg/L) respectively for treatments B and A, the ratio (F(B/A)) was of 1.1 with a C.I. of 0.90-1.24. For Cmax with means+/-SD of 3.1+/-0.6 (treatment B) and 3.2+/-0.8 mg/mL (treatment A), the ratio was 1.0. with C.I. of 0.92-1.08. The two treatments evidenced no significant differences in AUC(0-inifnity) and Cmax values and the two-one sided t-test showed that the two preparations are bioequivalent. There was no significant difference in Tmax between the liquid and tablets. Nelfinavir suspension might be a option for treating HIV-infected patients with swallowing disturbances or compliance problems.

To define the pharmacokinetic profile of efavirenz (EFV) in HIV-1 infected patients, when administered alone or with nelfinavir (NFV).Eleven HIV-positive patients, in steady-state treatment with EFV and 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interval. Plasma concentrations of EFV were determined by h.p.l.c.No significant difference was found between the principal pharmacokinetic parameters of EFV when administered alone or in combination with NFV (mean AUC: 57.1-7727.3 vs 60.9+/-12.3 microg ml-1 h; mean CL/F: 0.18+/-0.072 vs 0.16+/-0.04 l h-1 kg-1; mean Cmax: 4.0+/-1.7 vs 4.3+/-1.2 microg ml-1, and mean tmax: 4.1+/-1.7 vs 3.5+/-0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64+/-0.93 microg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24h) (r=0.96; P0. 01).Despite the common metabolic pathway, there was no significant influence of NFV on the pharmacokinetics of EFV. EFV exhibits a relatively low interindividual variability and a dosing regimen of 600 mg day-1 assures plasma concentrations that are adequate for inhibition of viral replication.

Tuberculosis in human immunodeficiency virus (HIV)-infected patients may act as a cofactor that accelerates the clinical course of HIV infection, and, indeed, HIV-infected patients with tuberculosis have a reduced survival rate compared to those without tuberculosis. Diagnosis of tuberculosis in HIV-positive patients can be difficult because of nonspecific symptoms and the time required for the identification of mycobacteria by means of culture techniques. Recently, antiretroviral combination therapies have improved the outcome of several acquired immune deficiency syndrome (AIDS)-associated conditions. Unfortunately, the use of antiretroviral therapy for patients coinfected with HIV and Mycobacterium tuberculosis is still to be fully evaluated. The complexity of side-effects due to antituberculosis medication and drug interaction represent important issues and combining an effective anti-HIV treatment with antituberculosis therapy is still a clinical challenge. We discuss here a case of spleen tuberculosis in a human immunodeficiency virus-positive patient who had a successful response after a diagnostic splenectomy and medical treatment that included classical antituberculosis treatment associated with antiretroviral therapy without protease inhibitors.

Diplopia is one of the neuro-ophthalmic manifestations that can be observed during HIV-infection. The etiologic agents of diplopia in HIV-positive patients can be identified with HIV itself or opportunistic pathogens or other related conditions. We reviewed the clinical records of 13 HIV-positive patients with mono or bilateral diplopia, focusing on etiologic agents, clinical evaluation and prognosis. This review encompassed all cases observed from January 1992 to June 1995 at the Infectious Diseases Department, Policlinico S. Matteo, University of Pavia. All patients underwent a complete ophthalmologic examination, including visual acuity, anterior segment evaluation with biomicroscopy, dilated indirect ophthalmoscopy and ocular motility evaluation (with Cover test and Hess-Lancaster test). If requested by clinical findings, radiologic (TC and/or MRI) and cerebrospinal fluid examination were performed in some patients. The most common causes of diplopia-CNS lesions or ocular diseases-, resulted in agreement with those reported in the literature (T. gondii, C. neoformans, non-Hodgkin lymphomas, HIV, JC virus, CMV). We were able to confirm, according to our experience, that diplopia occurrence is often a negative prognostic factor, since it is commonly associated with CNS conditions. In most cases diplopia can herald a near demise (8 patients on 13 died with 60 days from diplopia onset). In those cases where a treatment was available (2 cases of cryptococcosis, 1 case of neurotoxoplasmosis and 1 case of CMV retinitis) a complete resolution of neuro-ophthalmic symptoms was achieved.

The number of subjects with HIV infection or full-blown Acquired Immunodeficiency Syndrome (AIDS) is increasing throughout the world and the range of related opportunistic conditions (infections, neoplasms or degenerative disorders) is also increasing. Consequently, AIDS patients are likely to be prescribed a great number of different drugs. HIV infection is a progressive phenomenon, characterized by inevitable and often irreversible changes which may influence drug disposition, enhancing the risk of toxic adverse effects and drug interactions. One of the stages for the development of new agents and the establishment of an effective therapy is to conduct pharmacokinetic studies. Even though such studies are difficult to realize in AIDS subjects, the knowledge of altered pharmacokinetics of a drug in disease states offers an unique approach for improving and perhaps optimizing the therapeutic management. The purpose of this article is to review our current understanding of how HIV infection influences the various processes of drug disposition (i.e. absorption, distribution, metabolism and excretion).